Induction of Fas ligand (CD95L) by the toxic mistletoe lectins in human lymphocytes

Background: Fas ligand (FasL, CD95L) predominantly expressed on activated c ytotoxic T cells and NK cells triggers apoptosis in Fas receptor (Apo-1, CD 95),positive target cells. We investigated the expression of Fast, I:as and tumor necrosis factor (TNF) receptor 1 (TNF-R1, CD120a) on cultured human lymphocytes and leukemic T and B cells. Materials and Methods: Lymphocytes from six healthy individuals, from four patients with chronic lymphocytic T or B cell leukaemia, and leukemic Molt-4 cells were incubated with the apo ptosis- inducing mistletoe lectins (ML I and ML III). Results: Incubation o f differentiated lymphocytes with the ML resulted in a significant upregula tion of Fast in the surviving CD4(+) T helper cells, CD8(+) cells and CD19( +) B cells. Similarly, the TNF receptor expression increased, while the Fas molecule decreased. In contrast, Fast was not induced in leukemic cells. C onclusions: Apart from a direct induction of apoptosis in response to an in hibition of protein synthesis by the enzymic ML A chain, ML treatment may i ndirectly induce apoptosis in Fas(+) tumour cells through activated FasL(+) lymphocytes.